Neutrophil adhesion to activated endothelial cells and trans-endothelial migration of these cells are essential events of the innate immune response required for kill invading pathogens and bacterial clearance. While neutrophil recruitment into site of injury is the first-line of defense, excessive neutrophil infiltration and activation at the vessel wall is also the primary cause of inflammation and tissue damage. Neutrophils have been implicated in numerous inflammatory diseases such as acute lung injury, sepsis, and ischemia-reperfusion injury. Inhibition of β2 integrins using anti-β2 integrin antibodies has been shown to block adhesion of neutrophils to endothelial cells and prevent inflammation, leading to restored vascular integrity, which indicates that targeting neutrophils is a useful strategy in treating neutrophil-mediated inflammatory diseases. However, antibodies have the disadvantage of inducing generalized loss of neutrophil bactericidal function by impairing the ability of circulating neutrophils to adhere and migrate to the infected site.
Clearly, there is a demand for compositions and methods that permit targeting of activated neutrophils and treatment of neutrophil-mediated inflammatory diseases. The present invention satisfies this demand.